PROJECT SUMMARY Advanced age is associated with greater prevalence of cardiovascular disease (CVD) risk factors, adverse cardiac remodeling including left ventricular hypertrophy and concentric remodeling, often resulting in cardiac systolic and diastolic dysfunction. Such manifestations of pre-clinical disease may be due to molecular and cellular abnormalities that change throughout the human lifespan, with the culmination of clinical CVD, including heart failure, and mortality. Further knowledge of the biologic mechanisms of healthy aging is crucial to promote strategies for maintaining health into advanced ages. The study of small molecules has shown significant promise to identify key biologic mechanisms of disease processes, even predicting future disease. Recent studies using metabolomics, by our group and others, have provided insight into several biological pathways through the study of differential metabolite expression, suggesting mechanisms of CVD and longevity. However, the mechanisms of healthy aging remain poorly understood. Our goals are to establish the role of small molecules in key biologic pathways of amino acid and lipid metabolism with healthy cardiovascular aging and cardiovascular risk stratification in older adults. Over the next 12-24 months, we will generate preliminary data for an R01 submission to expand the breadth of analyses beyond the targeted metabolome examined in this proposal. Using an unbiased approach in the future will enable deeper insight into biologic pathways protective of CVD through older ages. Ultimately, we hope that further understanding of the mechanisms of healthy and unhealthy cardiovascular aging will lead to improved methods of cardiovascular risk stratification as well as target modifiable therapies for patient care.